Expression changes of PTEN in aortic dissection diseased tissues and its relationship with contractile phenotypic protein of VSMCs
Objective To observe the expression changes of phosphatase and tension homolog(PTEN)in diseased tissues of patients with aortic dissection(AD)and AD mice,and to explore the relationship between its expression and the contractile phenotypic protein of vascular smooth muscle cells(VSMCs).Methods Six cases of diseased aortas(AD group)were collected from patients undergoing Stanford A-type surgery,along with 6 corresponding normal segments from donor hearts(control group).We utilized HE staining to observe aortic structure,EVG staining to detect elastic fiber dis-ruption,and Western blotting to examine the expression of PTEN,myosin heavy chain 11(MYH11)and α-smooth muscle actin(α-SMA).Additionally,12 male C57BL/6J mice aged 3-4 weeks were randomly divided into the control and AD groups,with 6 mice in each group.Six male mice with vascular smooth muscle-specific knockout of PTEN were selected as the PTENCKO group.To establish the AD model,mice in the AD group and the PTENCKO group were fed with a diet contain-ing 0.25%β-aminopropionitrile for 4 weeks,followed by subcutaneous infusion of AngⅡ at a dose of 1000 ng/(kg·min)for 2 consecutive days.Mice in the control group were fed with a normal diet,and after 4 weeks,an equal volume of nor-mal saline was subcutaneously injected.After euthanasia,aortic tissues were collected,and Western blotting was per-formed to detect PTEN,MYH11,α-SMA,and autophagy-related proteins LC3Ⅱ/Ⅰ,Beclin-1,and p62.Results In the control group,the vascular wall tissue structure was clear,with orderly cell arrangement and neatly arranged elastic fi-bers in the vascular wall.However,in the AD group,the structure of the vascular wall was unclear,with partial loss and disordered arrangement of cells,as well as disintegration and fracture of elastic fibers in the vascular wall,accompanied by increased collagen deposition.Compared with the control group,the expression of PTEN protein in the aortic tissues in-creased in the AD group,while the expression levels of MYH11 and α-SMA proteins decreased(all P<0.05).Compared with the control group,the expression of PTEN,LC3Ⅱ/Ⅰ,and Beclin-1 protein in the aortic tissues increased in mice of the AD group,while the expression levels of MYH11,α-SMA,and p62 protein decreased(all P<0.05).Conversely,compared with the AD group,mice in the PTENCKO group showed decreased expression levels of PTEN,LC3Ⅱ/Ⅰ,and Beclin-1 protein in the aortic tissues,while the expression levels of MYH11,α-SMA,and p62 protein increased(all P<0.05).Conclusions PTEN is highly expressed in diseased tissues of AD patients and AD mice.Inhibiting PTEN can effectively alleviate autophagy,restore the expression of vascular contraction phenotype protein,and help to attenuate aortic medial degeneration.
phosphatase and tension homologaortic dissectionaortic medial degenerationautophagy
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